Several substituted 2-(2-pyridylmethyl)sulfinyl-1H-benzimidazoles are known gastric proton pump inhibitors. These include omeprazole (5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole), lansoprazole (2-[[[3-methyl-4-(2,2,2-trifluoro-ethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole), pantoprazole (5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole, and rabeprazole (2-[[[4-(3-methoxy-propoxy)-3-methyl-2-pyidinyl]methyl]sulfinyl]-1H-benzimidazole. For example, omeprazole is a proton pump inhibitor commercially available for the treatment of gastric ulcers. The compound is disclosed in European Patent No. 5318.
The reported synthesis of these substituted 2-(2-pyridylmethyl)sulfinyl-1H-benzimidazoles principally involves generally an oxidation process of a thioether moiety to form a thioester moiety of the compound of formula A:

Various methods employing various different oxidants to perform this oxidation are known. For example, Canadian Patent No. 1,263,119 describes the use of hydrogen peroxide over a vanadium catalyst (such as vanadium pentoxide, sodium vanadate and vanadium acteylacetonate). Canadian Patent No. 1,127,158 similarly describes the use of peracids, peresters, ozone, etc. European Patent Application, Publication No. 533,264 describes the use of magnesium monoperoxyphthalate as the oxidizing agent. PCT Publication No. WO91/18895 describes the use of m-chloroperoxy benzoic acid as the oxidizing agent. GB Pat. No.2,069,492 generally describes this acid and other peroxy acids in the oxidation of substituted (phenylthiomethyl)pyridines.
Use of tert-butyl hydroperoxide (TBHP) as an oxidant has already been suggested for the performance of various organic oxidations. Sharpless et al., Aldrichimica Acta 12:63 (1979) review the use of THBP as an oxidant and compared with hydrogen peroxide and other peracids. Sharpless et al. describe the use of TBHP in the epoxidation of olefinic alcohols in the presence of VO(acac)2 or Mo(CO)5 catalysts. The oxidation of sulphides, however, is not described.
In an effort to develop a method for the selective oxidation of sulphides to sulphoxides, Choudray et al., J. Mol. Catalysts, 75:L7–L12 (1992) describe the use of TBHP in the presence of vanadium pillared clay. The results demonstrated selectivity for the oxidation to sulphoxide in preference to the sulphone far superior to that of known TBHP/vanadium catalysts. The use of VO(acac)2 or V2O5 resulted in sulphones rather than sulfoxide predominating in the final product.
There has been a long felt need for efficient and safe methods for the selective oxidation of a thioether moiety of formula B to a thioester moiety of formula A. The present invention provides efficient and safe methods of preparing various substituted 2-(2-pyridylmethyl)sulfinyl-1H-benzimidazoles.